The Magic Drug Recedes: Who Will Reign in the Over $400 Billion New Oncology Battlefield?
Text | Yixian Insight, Author: Zhang Xiaoman
Ten years ago, PD-1/PD-L1 inhibitors opened a new door for cancer treatment.
It was like a key unlocking the immune system, disengaging the "brake" mechanism of immune cells, and also opening a new era of wealth for the global innovative drug industry.
"Keytruda" and "Opdivo" achieved annual sales of tens of billions of dollars, and China's first-generation biotech companies also leveraged this wave to make a collective debut on the global pharmaceutical stage.
But no wave can surge forever.
Today, the development bottlenecks of PD-1 have become clearly apparent: At the clinical level, the response rate of monotherapy has hit a ceiling; at the commercial level, the number of entrants continues to increase, and price wars keep escalating.
The once "magic anticancer drug" is gradually becoming a basic therapy in the tumor treatment system.
The core question that follows is: When PD-1's "old ticket" gradually fails, who can get the ticket for the next decade of cancer treatment?
The answer has already surfaced in the global mergers and acquisitions and strategic layouts of multinational pharmaceutical companies: Bispecific antibodies, trispecific antibodies, and T-cell engagers (TCEs) are becoming the core tracks of a new round of industry competition.
These drugs are no longer limited to a single target's linear breakthrough but attempt to achieve multiple immune modulations within a single molecule. According to a forecast by CIC Consulting, the global oncology drug market size is expected to grow from $262.1 billion in 2024 to $724.9 billion in 2035.
Data source: CIC Consulting
Facing a market increment of over $400 billion, the industry is not seeking the next "PD-1" but a new underlying logic for tumor treatment.
The Magic Drug Recedes: PD-1 Falls into the Deep Water of Price Wars
To understand why bispecific and multispecific antibodies have suddenly become industry focuses, we must first look at the real predicament of the monoclonal antibody track—its pressure comes not from a single link but from a double squeeze at both clinical and commercial ends.
First, the bottleneck at the clinical end has long been evident.
The objective response rate (ORR) of a single PD-1 inhibitor in most solid tumors is only 20%-30%, and a large number of patients have primary or secondary drug resistance.
Especially for "cold tumors" lacking immune cell infiltration, such as colorectal cancer and pancreatic cancer, single-target drugs often struggle to exert effective effects.
Second, competition at the commercial end has entered an overheated red sea.
Take the systematic treatment of hepatocellular carcinoma (HCC) as an example: over 10 PD-1 inhibitors have been approved globally, with multinational pharmaceutical companies competing head-to-head with domestic companies like Hengrui Medicine, BeiGene, Innovent Biologics, and Junshi Biosciences; in head and neck squamous cell carcinoma (HNSCC), there are also 5 PD-1 products in direct competition.
Data source: Official WeChat accounts of various companies and public information on the internet
When more than a dozen heavyweight players crowd into a single track, the technology premium is quickly diluted.
The innovative drug industry is thus pushed into the deep water of "price-for-volume" in national medical insurance negotiations and volume-based procurement. The price drop is no longer an accidental market fluctuation but an inevitable trend under the structural transformation of the industry.
Financial data most intuitively reflect this pressure. Due to factors such as medical insurance cost control and intensified market competition, the prices of multiple core monoclonal antibody products have dropped significantly. For example, the average selling price of a commercialized monoclonal antibody product fell from 2,022.1 RMB to 1,786.1 RMB within one year.
This is the "midlife crisis" of the monoclonal antibody era: In terms of efficacy, the ceiling has not been effectively broken; in terms of business, profit margins have been continuously compressed by competition and cost control.
For companies, developing next-generation molecular drugs is no longer just about pursuing scientific breakthroughs—it is a necessary choice for survival.
Bispecific Antibodies Take the Baton: Becoming the New Core of Tumor Treatment
If the core role of PD-1 monoclonal antibodies is to "release the brakes" on the immune system, then the goal of bispecific antibodies is to simultaneously release the brakes and clear a path for immune cells to attack tumors.
It is not a simple superposition of two monoclonal antibodies but a redesign of the immune response in terms of time and space.
PD-1/VEGF bispecific antibodies are the most watched direction in this technical route.
In the past, clinical practice often used a combination therapy of "PD-1 monoclonal antibody + anti-angiogenic targeted drugs"; bispecific antibodies integrate these two effects into the same molecule: one end inhibits tumor angiogenesis via anti-VEGF, promoting vascular normalization in the tumor microenvironment while reducing immunosuppressive factors; the other end relieves tumor immune escape via anti-PD-1, allowing T cells to enter tumor tissue more efficiently.
This is why non-small cell lung cancer (NSCLC) has become a key battlefield for testing the clinical potential of bispecific antibodies.
Indeed, the industry inflection point where bispecific antibodies replace monoclonal antibodies has arrived.
The industry's confidence in bispecific antibodies stems from a decisive clinical showdown in the past two years: a PD-1/VEGF bispecific antibody developed by a domestic company, represented by Akeso, defeated the industry-dominant Keytruda in a head-to-head Phase 3 clinical trial for advanced non-small cell lung cancer.
This landmark victory established a new consensus in oncology in 2026: bispecific antibodies are no longer a fallback option after monoclonal antibody resistance; they can substantially take over first-line treatment and rewrite clinical guidelines as a new gold standard.
Driven by this consensus, subsequent companies are pushing for higher efficacy ceilings through optimized molecular design.
Take SCTB14, a PD-1/VEGF bispecific antibody candidate disclosed by Sinocelltech, as an example. In patients with third-line or advanced non-small cell lung cancer who had not previously received immune checkpoint inhibitors, the drug achieved a 44% objective response rate (ORR), a median progression-free survival (PFS) of 6.9 months, and a 10-month overall survival (OS) rate of 88% as monotherapy; in first-line NSCLC patients with TPS ≥ 10%, SCTB14 achieved a confirmed ORR of 65%, a disease control rate (DCR) of 100%, and a 12-month OS rate of 82%.
Thus, the value of bispecific antibodies goes far beyond "adding one more target."
It truly reconstructs the underlying logic of tumor treatment: In the past, monoclonal antibodies were the treatment platform, and combination therapies were just supplementary; now, multi-target synergy is directly built into the molecular design.
If this trend is continuously validated by clinical data, bispecific antibodies are expected to upgrade from a supplementary option to a core solution in the treatment of multiple solid tumors, becoming the foundational base for the next generation of cancer therapy.
Trispecific Antibody Breakthrough: Advancing into the Uncharted Territory of Immunotherapy
Bispecific antibodies have opened a new door for cancer treatment, but the hardest-to-treat tumor challenges still lie deeper.
"Cold tumors" such as colorectal cancer, pancreatic ductal adenocarcinoma, and biliary tract cancer have long been poorly responsive to immunotherapy. The reason is not only the scarcity of immune cells in tumor tissue but also the complex immunosuppressive network in the tumor microenvironment.
Among them, immunosuppressive ligands like TGF-β act as a "protective shield," not only blocking immune cells from approaching the tumor but also potentially leading to dual resistance to angiogenesis inhibitors and immunotherapy.
To break through this barrier, a single target is far from enough, and even dual targets may not be fully effective.
In this context, trispecific antibodies are being pushed to the forefront of the industry.
SCTB41, a PD-1/VEGF/TGFβRII trispecific antibody developed by Sinocelltech, is a typical example of this research approach.
It integrates three functions simultaneously: PD-1 relieves immune brakes, VEGF cuts off tumor blood vessels and blocks related immunosuppressive pathways, and TGFβRII is used to break through deeper immune barriers.
More notably, this type of trispecific antibody has shown preliminary breakthrough efficacy in second-line or later patients with extremely difficult-to-treat "cold tumors" such as colorectal cancer, biliary tract cancer, and pancreatic ductal adenocarcinoma.
Among enrolled patients, 54% had received prior immunotherapy; SCTB41 still achieved a 22% unconfirmed ORR (uORR) and an 81% unconfirmed DCR (uDCR); even in the "immune desert" population with very low PD-L1 expression (TPS < 1%), the ORR reached 38% and DCR reached 88%.
The significance of these data is not that they provide a final treatment answer, but that they demonstrate antibody engineering technology is moving from "single-target blockade" to "multi-target precise regulation."
Future industry competition may no longer be about who can first discover a new target, but who can integrate multiple targets into a stable, efficient, and scalable molecular system.
TCE Crosses Boundaries: From an Anticancer Weapon to a New Hope for Autoimmune Diseases
If trispecific antibodies represent a "precision battle" against the tumor microenvironment, then T-cell engagers (TCEs) offer a more direct treatment approach.
Taking CD20/CD3 TCE (a T-cell-engaging bispecific antibody) as an example, its mechanism of action is like building a bridge: one end specifically binds to disease-causing B cells, and the other end recruits the body's own T cells, forcing the two into close contact, thereby achieving precise killing of disease-causing cells by T cells.
This mechanism was originally a "trump card" in the field of hematologic tumor treatment.
Data showed that a CD20/CD3 TCE (SCTB35) achieved a 100% unconfirmed ORR in target dose groups for diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL).
As of May 2026, five CD20/CD3 TCEs have been approved globally, of which three have been approved in China: Roche's mosunetuzumab (brand name: Glofix/Columvi) for relapsed/refractory follicular lymphoma (approved in China in December 2024); epcoritamab (brand name: Epkinly), jointly developed by AbbVie and Genmab, for relapsed/refractory follicular lymphoma and DLBCL (approved in China in May 2026); and Roche's glofitamab for relapsed/refractory DLBCL (approved in China in November 2023).
Data source: Public information on the internet
The greater imaginative space for TCE technology lies in its cross-border application.
Currently, this technology is being extended to the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE).
Systemic lupus erythematosus is known as the "incurable cancer," characterized by high recurrence rates and treatment difficulty. Compared with traditional monoclonal antibodies, TCE's potential advantage lies in its ability to more directly and efficiently clear pathogenic B cells that produce autoantibodies, and it may also promote the formation of immune memory, thereby reducing the risk of disease recurrence.
In a Phase Ib clinical trial for SLE, after a single dose at a very low dose in some patients, peripheral blood B cells were rapidly reduced to a state of "near-complete depletion," and this low level was maintained for up to 24 weeks; among all 30 patients receiving different doses, the overall Physician Global Assessment (PGA) response rate at week 4 reached 100%, and the mean SLE Disease Activity Index (SLEDAI) response rate at week 24 reached 71%.
This is the core reason why both capital and the industry are paying attention to TCEs.
It is predicted that the global immune and inflammation (I&I) drug market size will reach $412.4 billion by 2035.
Data source: CIC Consulting
Migrating the redirected immune anticancer technology to the trillion-yuan autoimmune disease track is expected to become an important direction for generating "super blockbuster" drugs in the next 5 to 10 years.
The Decisive Factor: The Moat Hidden in the Production Workshop
However, the more complex the molecular structure, the more the industry competition becomes not just a scientific contest.
Bispecific antibodies, trispecific antibodies, and TCEs paint a promising clinical blueprint, but what truly determines whether they can be commercially translated is often the invisible production workshop.
The development of multispecific antibodies is essentially a discipline of extreme engineering.
Integrating the antibody structures of two or three different functions into the same molecule can easily lead to problems such as light chain mispairing, protein aggregation, and low expression levels.
A molecule may appear perfect in laboratory papers and business roadshows, but if the mass production cost exceeds the market acceptable price, it cannot become a truly commercial product.
This means that the asset-light operational logic prevalent in the monoclonal antibody era is no longer fully applicable in the multispecific antibody era.
Especially in recent years, geopolitical factors such as the overseas "Biosecure Act" have fermented, and the global pharmaceutical supply chain is undergoing profound restructuring. The asset-light model that relies heavily on external single CXO contract manufacturing has fully exposed its compliance risks and supply chain fragility.
In the future, large and self-controllable production capacity reserves, complete and coherent underlying production processes, and internalized supply chain systems will become the core foundation for enterprise survival and development.
Therefore, whoever can raise the cell expression level of multispecific antibodies to that of monoclonal antibodies (e.g., above 5 g/L) through innovative processes and compress production costs to the industry-leading level will hold absolute initiative in the stringent domestic medical insurance cost-control environment and complex global outbound competition.
This also sounds an alarm for the entire industry: In the next decade, innovative drug companies cannot only excel at telling molecular stories.
Whoever can stably mass-produce complex molecular designs and keep costs within a commercially viable range will truly build an unassailable moat.
Looking back at the past decade, fast-follow was once a viable development path.
At that time, market increments were ample, overseas targets were clearly validated, and domestic companies could carve out a place in tracks like PD-1 as long as they were fast enough and had strong execution.
But as similar drugs flooded in and medical insurance cost control deepened, the dividends of pure follow-up have completely disappeared.
A new logic of industry competition has taken shape: On the front end, companies must dare to engage in global competition for first-in-class and best-in-class; on the back end, they must have a strong production and manufacturing system and cost control capabilities to turn scientific ideas into sustainable commercial products.
Returning to the initial question: After PD-1, who can get the next ticket?
The answer may belong to those "hexagonal warriors"—those who can break through the clinical efficacy ceiling with cutting-edge mechanisms and, at the same time, hold the cost bottom line with an advanced manufacturing platform.
Undoubtedly, bispecific antibodies, trispecific antibodies, and TCEs are not the end of tumor treatment, but they have clearly pointed the direction for the next voyage of Chinese biotech companies.
